The role of the English Surveillance Programme on Antimicrobial Use & Resistance in improving stewardship Susan Hopkins Consultant Infectious Diseases & Microbiology, Royal Free Healthcare Epidemiologist, Public Health England Hon Snr Lecturer, UCL

UK AMR Strategy: Seven Key Areas for Action Improving infection prevention and control practices Optimising prescribing practice Improving professional education, training and public engagement Developing new drugs, treatments and diagnostics Better access to and use of surveillance data Better identification and prioritisation of AMR research needs Strengthened international collaboration Action in all of the above areas is needed simultaneously. The

Antimicrobial stewardship programmes aim to improve quality of prescribing usage data required to monitor impact must be related to AMR epidemiology BUGS DRUGS AMR

PHE ESPAUR: English Surveillance Programme for AMU & AMR Support antimicrobial stewardship by monitoring antimicrobial use Monitor key drug-bug combinations Enhance data analysis and advice on use of carbapenemens & critically important drugs Develop & measure quality measures for optimal antimicrobial prescribing Develop methods to monitor the clinical outcomes/ unintended consequences Develop initiatives to change public and professional behaviour Input into national antimicrobial guidance

Top 6 Blood stream infections, Voluntary surveillance, 2002-11

Staphylococcus aureus: MRSA & MSSA Lowest number of MRSA bacteraemias in over 15 years

Escherichia coli bacteraemia Year on year increase over last 10 years – approx 20,000 more than 15 years ago 25% were diagnosed ≥2 days after hospital admission Increased AMR in hospital associated cases

Resistance in E coli, Blood, 2004-2013 N~30,000/year Resistance in Klebsiella, Blood, 2004-2013 N~8,000/year Is this change in resistance important – empiric gudielines in hospitals are usually augmentin/ taz/ gent for sepsis. This means 1 in 10 people get an inappropriate first antibiotic – likely 3-4 fold increased risk of death. Why have these changes occurred – earlier I showed you the graph demosntrating a fall in AMU quinolones and Declines in resistance to Ciprofloxacin & Ceftriaxone Increases in resistance to Piperacillin-Tazobactam & Carbapenems ? Ecological Pressure

Rapid spread of resistance AMR is a global problem – and increasing international travel only reinforces this. This is an example, showing how quickly NDM1 resistance spread around the world within months: NDM1 is New Delhi metallo-beta-lactamase 1 (an enzyme that makes bacteria resistant to beta lactams like carbopenems) First found in a patient in New Delhi in December 2009 (in a Swedish national who was visiting India). Within 12 months, had been detected in 17 further countries: Norway, Finland, Sweden, Holland, UK, France, Spain, Denmark, Belgium, Germany, Austria, Pakistan, Oman, Kenya, Japan, USA and Australia. --- Original source: Nature, 13th July 2013 Antimicrobial resistance Image from slides produced by McKinsey & Company, based on earlier image from Nature, 13th July 2013

PHE confirmed carbapenemase producers

Changes 2007-2012 Over the last 5 years, The fall over the last five years in hospital prescribing of cephalosporins and quinolones has been mirrored by a comparable fall in community antibiotic prescriptions. The number of community prescription items for cephalosporin’s in the last five years has fallen by 55% and that of quinolones by 36% (up to 2012 – 49% & 35% respectively) In contrast - number of prescriptions for tetracyclines, macrolides, trimethoprim and macrodantin (first line antibiotics recommended by National guidance) have increased. The reductions in the use of quinolones and cephalosporins are part of the antimicrobial stewardship measures that have been in place nationally, in the drive to reduce Clostridium difficile infections. Trends in Prescribing of Antibacterials , excluding penicillins, in General Practice in England AMP Key Trends Diane Ashiru-Oredope

AMP Key Trends Diane Ashiru-Oredope

AMP Key Trends Diane Ashiru-Oredope

Secondary care data from Cooke et al via IMS Health shows that from 2007/8 to 2011/12: Use of cephalosporins and quinolones have reduced by 38% (1st, 2nd & 3rd generation cephalosporins) and 24% respectively whilst Use of co-amoxiclav, carbapenems and piperacillin/tazobactam have increased by 56·6%, 94·8% and 142·3% respectively

Carbapenem usage for English Hospitals, 2007-2012 Looking a little bit more closely at carbapenem use demonstrates a year on year rise (chicken or egg) – overally use has doubled

Carbapenem usage as % of total use in English hospitals in 2011-2012

UCLp Hospitals & Point Prevalence Survey First national prevalence antimicrobial use survey 2011 Many UCLp hospitals participated Overall England Prevalence 35% Variation across hospital type Variation with age, sex, comorbidity, specialty, history of surgery

Point prevalence Survey: Antimicrobial use AMP Key Trends Diane Ashiru-Oredope

Variation in AMU prevalence, SAUR Hospital Crude AMU Prevalence % (95% CI) 1 32.3 (27.1-37.9) 2 39.9 (34.6-45.5) 3 43.8 (39.8-48.0) 4 31.5 (28.3-35.0) 5 41.8 (36.8-47.1)

Proportion of AMU by drug National 1 2 3 4 5 Co-amox 13.8 26.7 23.1 22.8 14.7 Pip-tazo 10.9 5.8 11.5 12.8 11.3 24.1 Gent 4.2 6.7 1.9 2.3 4.5 Mero 5.0 (8th) 0 (>20th) 2.6 (10th) 3.8 (7th) 6.8 (4th) 9.5 (3rd)

Can use influence national AMR? Until 2007, major increases in cephalosporin and quinolone resistance amongst Escherichia coli & Klebsiella spp Plateau/ fall in resistance was from 2007 (LabBase / BSAC) Fall in resistance coincides with the large reduction in cephalosporin and quinolone use due to national antimicrobial stewardship guidance to reduce Clostridium difficile infections nationally Replacement have been penicillin/b-lactamase inhibitors which may have another impact Livermore D M et al. J. Antimicrob. Chemother. 2013;jac.dkt212 Until 2007, the UK saw major increases in cephalosporin and quinolone resistance amongst Escherichia coli and Klebsiella spp Plateau/ fall in resistance was from 2007 (LabBase and BSAC data) Fall in resistance coincides with the large reduction in cephalosporin and quinolone use due to national antimicrobial stewardship guidance to reduce Clostridium difficile infections nationally Replacement have been penicillin/b-lactamase inhibitors which may be adding to the selection for carbapenamase producers Livermore D M et al. J. Antimicrob. Chemother. 2013;jac.dkt212 The UK saw major increases in cephalosporin and quinolone resistance amongst Enterobacteriaceae from 2001 to 2006, subsequent trends LabBase and BSAC data showed that rates of non-susceptibility to cephalosporins and quinolones rose amongst Escherichia coli and Klebsiella spp. until mid-decade (2004–07) before amongst Escherichia coli and Klebsiella spp. until mid-decade (2004–07) before plateauing or falling They coincided with large reductions in hospital cephalosporin and quinolone use, owing to concern about Clostridium difficile, with replacement by penicillin/b-lactamase inhibitor combinations, which have borderline activity against ESBL producers, but consistently lack activity against carbapenemase producers. Non-susceptibility to cephalosporins and quinolones has declined among bloodstream Enterobacteriaceae in the UK, probably reflecting prescribing shifts. The penicillin/b-lactamase inhibitor combinations that have largely replaced cephalosporins and quinolones may add to selection for carbapenemase producers. have largely replaced cephalosporins and quinolones may add to selection for carbapenemase produce The changes in prescribing across primary and secondary care may, at least in part, explain the increase of Escherichia coli bacteraemias and emergence of other MDR clones.

Conclusion AMR major threat to future healthcare AMU recognised driver of resistance ESPAUR a national surveillance programme developed by PHE will focus on integrating data develop & measure quality measures UCLp key role working across hospitals to support initiative validate data and be a national leader You can’t make an omelette without cracking an egg.

Acknowledgements: Diane Ashire-Oredope Jonathan Cooke Sue Faulding Russell Hope Alan Johnson Cliodna McNulty Pete Stephens Neil Woodford GPs, microbiology, pharmacy, infection prevention & control teams